The most well-known form of familial thyroid cancer is hereditary medullary thyroid carcinoma (MTC). This neoplasm is often associated with pheochromocytoma and hyperparathyroidism, a combination known as the multiple endocrine neoplasia syndrome type 2A (MEN 2A). The rare association of MTC and pheochromocytoma with multiple mucosal neuromas is called multiple endocrine neoplasia syndrome type 2B (MEN 2B). Of those who present with clinical signs and symptoms, almost half die of the disease and others may suffer significant morbidity. By contrast, early diagnosis by screening of family members allows for treatment with thyroidectomy and/or adrenalectomy, which are often curative. Measurement of serum calcitonin before and after stimulation with pentagastrin and/or calcium is mandatory for the diagnosis of MTC. Testing of first-degree relatives of patients with MTC should be started by the age of 3 to 5 years. In families with the MEN 2B syndrome, screening should be started during the first year after birth and include a search for the characteristic phenotype. The mapping of the MEN 2A gene to the centromeric region of chromosome 10 has provided an alternative approach to the diagnosis of MEN 2A gene carriers. Genetic screening using linked markers can now be done with an accuracy of 95% in informative families. Surgery is the treatment of choice for cases of MEN 2, but the extent of surgical resection of the involved endocrine organs is still a subject of debate.(ABSTRACT TRUNCATED AT 250 WORDS)